title: Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL, ABCB1, OPRM1) with opioid dependence in European population: a case-control study.
abstract: It is becoming increasingly evident that genetic variants contribute to the development of opioid addiction. An elucidation of these genetic factors is crucial for a better understanding of this chronic disease and may help to develop novel therapeutic strategies. In recent years, several candidate genes were implicated in opioid dependence. However, most study findings have not been replicated and additional studies are required before reported associations can be considered robust. Thus, the major objective of this study was to replicate earlier findings and to identify new genetic polymorphisms contributing to the individual susceptibility to opioid addiction, respectively. Therefore, a candidate gene association study was conducted including 142 well-phenotyped long-term opioid addicts undergoing opioid maintenance therapy and 142 well-matched healthy controls. In both study groups, 24 single nucleotide polymorphisms predominantly located in pharmacogenetic candidate genes have been genotyped using an accurate mass spectrometry based method. The most significant associations with opioid addiction (remaining significant after adjustment for multiple testing) were observed for the rs948854 SNP in the galanin gene (GAL, p = 0.001) and the rs2236861 SNP in the delta opioid receptor gene (OPRD1, p = 0.001). Moreover, an association of the ATP binding cassette transporter 1 (ABCB1) variant rs1045642 and the Mu Opioid receptor (OPRM1) variant rs9479757 with opioid addiction was observed. The present study provides further support for a contribution of GAL and OPRD1 variants to the development of opioid addiction. Furthermore, our results indicate a potential contribution of OPRM1 and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it seems important that these genes are addressed in further addiction related studies.
authors.affiliation: Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Beate
authors.initials: B
authors.lastname: Beer
authors.forename: Robert
authors.initials: R
authors.lastname: Erb
authors.forename: Marion
authors.initials: M
authors.lastname: Pavlic
authors.forename: Hanno
authors.initials: H
authors.lastname: Ulmer
authors.forename: Salvatore
authors.initials: S
authors.lastname: Giacomuzzi
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Riemer
authors.forename: Herbert
authors.initials: H
authors.lastname: Oberacher
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005060:Europe; D019004:Galanin / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry; D016017:Odds Ratio; D009293:Opioid-Related Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017465:Receptors, Opioid, delta / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C056567:GAL protein, human; C529706:OPRD1 protein, human; C485764:OPRM1 protein, human; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D019004:Galanin